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Objective: To compare the impact of sertindole and haloperidol on cognitive function in patients suffering from schizophrenia., Methods: In a 12 week trial, of the 40 patients randomised to treatment, 34 (17 sertindole and 17 haloperidol) were included in the analysis set. Cognitive sub-processes were investigated with the Reaction Time Decomposition (RTD) method and the Wisconsin Card Sorting Test (WCST), at baseline, Week 4 and Week 12., Results: In executive function, i.e. set shifting tasks, sertindole reversed cognitive deficits significantly more than haloperidol. It was demonstrated that this atypical drug improved cognitive processing independently of motor function. Patients receiving sertindole markedly improved on the RTD task at Week 4 and continued to improve (although at a slower rate) at Week 12, those patients receiving haloperidol showed marked impairment at Week 4 with partial recovery by Week 12., Conclusion: The study demonstrated two distinct processes of action on cognition between sertindole and haloperidol and the marked beneficial effects of sertindole, particularly in parameters that are regarded as schizophrenia-related cognitive disturbances.

Cognitive impairment in schizophrenia must be seen as a disturbance of cortico-sub-cortical connectivity with a neurotransmitter imbalance in a circuitry system, which connects thalamic input with prefrontal processing and supplementary motor cortex and basal ganglia output. The concept of maze-solving behaviour as a continuous cognitive task evoking a conflict between prefrontal cortex and basal ganglia activity is explained and introduced to distinguish between the effects of D2 blocking agents and substances with a predominant 5HT2A receptor affinity, such as clozapine and risperidone. Complex mazes show a cognitive deficit in untreated schizophrenic patients that are impaired by conventional and improved by atypical antipsychotic substances. Processing speed improves most on clozapine, while parallel processing is best supported by the non-sedative atypical substance risperidone. Maze paradigms are presented.

Background: The effectiveness of antipsychotic drugs against positive psychotic symptoms has been demonstrated in many studies, but their effects on quality of life have yet to be clarified. The impact of different neuroleptic therapies on the subjective quality of life of schizophrenic patients is evaluated in a cross-sectional open study., Method: During a four-month period a standardised quality of life interview for schizophrenic patients was applied on day 10 after admission; 33 patients on atypical neuroleptics (AAP) were compared with 31 matched patients on conventional neuroleptics (CAP)., Results: The AAP group had significantly higher scores in general quality of life as well as in different life domains: physical well-being, social life and everyday life. In separate comparisons of the AAP group, patients on clozapine and risperidone were found to have a higher quality of life score than patients on CAP or zotepine., Conclusions: The pharmacological profile of clozapine and risperidone may provide a basis for explaining the higher subjective quality of life found in this study. The lower quality of life of the CAP group may possibly be related to intrinsic effects of the conventional antipsychotics.

Clinical interest in the so-called atypical antipsychotics currently focuses on the possibility of improving the negative symptoms of schizophrenia and the cognitive dysfunction associated with the disease. While clozapine has been shown to be effective in this respect, no data are available on zotepine. We report on a double-blind randomized study designed to evaluate the impact of zotepine and clozapine on cognitive dysfunction in schizophrenia. Cognitive function was operationalized by a maze test in which patients traversed computer-displayed mazes of increasing complexity. Passage time, route, and motor errors were evaluated. 25 schizophrenic (DSM-IIIR) patients were included in each group. After washout, they were randomized on zotepine or clozapine and given up to 450 mg of substance each. Patients were followed for six weeks and evaluated weekly. We report on a subsample of 26 patients matched for baseline BPRS, SANS, and age. 13 matched healthy persons were recruited as controls. ANOVA with group and course over time as factors was used for analysis. Both clozapine and zotepine achieved a highly significant decrease in overall symptoms (BPRS) and negative symptoms (SANS). Zotepine and clozapine were equally effective. In the maze tests, motor errors in simple mazes were stable over time and differentiated schizophrenics from controls as a "trait" marker. In passage time and maze route, schizophrenics performed worse than controls. An improvement by medication was evident in both medication groups, but was more pronounced in the zotepine-treated group. The study confirms previous results on the efficacy of clozapine and zotepine in treating negative symptoms of schizophrenia. The data presented show for the first time that zotepine is efficacious in improving cognitive dysfunction, confirming this substance's value as an atypical antipsychotic.

Objective: In a companion paper we demonstrated that in reaction-time tasks the response selection stage is selectively disturbed in schizophrenia. The aim of the present study is the investigation of subprocesses, which are incorporated into repeatedly activated loops of cognitive processes and need additional information from working memory. Method: Maze tasks of varying complexity (with and without bifurcations) were presented to drug-naive and treated first-onset schizophrenic patients. The tasks had to be solved under easy and difficult motor-conditions. Both patient samples were compared with healthy control groups matched by age, sex, education and experience with the experimental setting. Results: In mazes with alternative routes patients exhibited the expected decrease of performance. However, untreated patients improved under difficult motor conditions. This improvement is smaller after neuroleptic treatment. Conclusion: Under difficult motor conditions attention is focused on the execution of movements and thus withdrawn from perceiving irrelevant response alternatives, i.e. the effects of disturbed response selection are reduced. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study is to demonstrate that deficits of information processing in schizophrenic patients can be isolated with reaction-time (RT) decomposition paradigms. Method: Three types of visually presented tasks were applied: simple, disjunctive and choice RT-tasks. RT were split into movement latency and time necessary to execute movements. Comparisons of three samples of schizophrenic patients (295.3) with individually matched (age, sex, education and handedness) healthy controls are presented: Sample 1: 10 drug-naive first-onset patients, Sample 2: 10 neuroleptically treated first-onset patients, Sample 3: 10 neuroleptically treated chronically ill patients. Results: Findings indicate that schizophrenia affects primarily subprocesses in which percepts are translated into appropriate actions (response-selection). Neuroleptic treatment improves processing at this stage but is accompanied by slowing of movement execution. Conclusion: Response-selection is selectively impaired in first-onset patients. This disturbance, which might be specific for schizophrenia, can be regarded as indication of a disconnection between frontal and posterior areas. [ABSTRACT FROM AUTHOR]